Cartia XT

WARNINGS

Cardiac Conduction

Diltiazem prolongs AV node refractory periods without significantly prolonging
sinus node recovery time, except in patients with sick sinus syndrome. This
effect may rarely result in abnormally slow heart rates (particularly in patients
with sick sinus syndrome) or second- or third degree AV block (13 of 3290 patients
or 0.40%). Concomitant use of diltiazem with betablockers or digitalis may result
in additive effects on cardiac conduction. A patient with Prinzmetal's angina
developed periods of asystole (2 to 5 seconds) after a single dose of 60 mg
of diltiazem. (See ADVERSE REACTIONS section.)

Congestive Heart Failure

Although diltiazem has a negative inotropic effect in isolated animal tissue
preparations, hemodynamic studies in humans with normal ventricular function
have not shown a reduction in cardiac index nor consistent negative effects
on contractility (dp/dt). An acute study of oral diltiazem in patients with
impaired ventricular function (ejection fraction 24% ± 6%) showed improvement
in indices of ventricular function without significant decrease in contractile
function (dp/dt). Worsening of congestive heart failure has been reported in
patients with preexisting impairment of ventricular function. Experience with
the use of diltiazem hydrochloride in combination with beta-blockers in patients
with impaired ventricular function is limited. Caution should be exercised when
using this combination.

Hypotension

Decreases in blood pressure associated with diltiazem therapy may occasionally
result in symptomatic hypotension.

Acute Hepatic Injury

Mild elevations of transaminases with and without concomitant elevation in
alkaline phosphatase and bilirubin have been observed in clinical studies. Such
elevations were usually transient and frequently resolved even with continued
diltiazem treatment. In rare instances, significant elevations in enzymes such
as alkaline phosphatase, LDH, SGOT, SGPT, and other phenomena consistent with
acute hepatic injury have been noted. These reactions tended to occur early
after therapy initiation (1 to 8 weeks) and have been reversible upon discontinuation
of drug therapy. The relationship to diltiazem is uncertain in some cases, but
probable in some. (See PRECAUTIONS.)

PRECAUTIONS

General

Diltiazem hydrochloride is extensively metabolized by the liver and excreted
by the kidneys and in bile. As with any drug given over prolonged periods, laboratory
parameters of renal and hepatic function should be monitored at regular intervals.
The drug should be used with caution in patients with impaired renal or hepatic
function. In subacute and chronic dog and rat studies designed to produce toxicity,
high doses of diltiazem were associated with hepatic damage. In special subacute
hepatic studies, oral doses of 125 mg/kg and higher in rats were associated
with histological changes in the liver, which were reversible when the drug
was discontinued. In dogs, doses of 20 mg/kg were also associated with hepatic
changes; however, these changes were reversible with continued dosing.

Dermatological events (see ADVERSE REACTIONS section) may be transient
and may disappear despite continued use of diltiazem. However, skin eruptions
progressing to erythema multiforme and/or exfoliative dermatitis have also been
infrequently reported. Should a dermatologic reaction persist, the drug should
be discontinued.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 24-month study in rats at oral dosage levels of up to 100 mg/kg/day and a
21-month study in mice at oral dosage levels of up to 30 mg/kg/day showed no
evidence of carcinogenicity. There was also no mutagenic response in vitro
or in vivo in mammalian cell assays or in vitro in bacteria. No evidence
of impaired fertility was observed in a study performed in male and female rats
at oral dosages of up to 100 mg/kg/day.

Pregnancy

Category C. Reproduction studies have been conducted in mice,
rats, and rabbits. Administration of doses ranging from five to ten times greater
(on a mg/kg basis) than the daily recommended therapeutic dose has resulted
in embryo and fetal lethality. These doses, in some studies, have been reported
to cause skeletal abnormalities. In the perinatal/postnatal studies there was
an increased incidence of stillbirths at doses of 20 times the human dose or
greater.

There are no well-controlled studies in pregnant women; therefore, use diltiazem
in pregnant women only if the potential benefit justifies the potential risk
to the fetus.

Nursing Mothers

Diltiazem is excreted in human milk. One report suggests that concentrations
in breast milk may approximate serum levels. If use of diltiazem is deemed essential,
an alternative method of infant feeding should be instituted.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of diltiazem did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from younger
subjects. Other reported clinical experience has not identified differences
in responses between the elderly and younger patients. In general, dose selection
for an elderly patient should be cautious, usually starting at the low end of
the dosing range, reflecting the greater frequency of decreased hepatic, renal,
or cardiac function, and of concomitant disease or other drug therapy.

Last reviewed on RxList: 1/19/2010
This monograph has been modified to include the generic and brand name in many instances.